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Aims: To fully elucidate the clinicopathological features of breast carcinoma in sclerosing adenosis (SA-BC)., Methods: Clinical and histological characteristics of 206 SA-BCs from 180 patients were retrospectively evaluated. Immunohistochemical phenotype was examined. The clinicopathological relevance of the topographical pattern of SA-BCs was analysed., Results: Overall, up to 46 patients (25.6%) had contralateral cancer, either SA associated or not. Of 99 cases who underwent core needle biopsy (CNB), 36 were underestimated as adenosis or atypical ductal hyperplasia at CNB, 5 invasive cases were misinterpreted as in situ carcinomas, whereas 4 ductal carcinoma in situ (DCIS) cases were overdiagnosed as invasive carcinoma. Microscopically, 163 tumours were in situ, including 136 DCIS, 19 lobular carcinomas in situ (LCIS) and 8 mixed DCIS/LCIS; of these carcinomas in situ (CIS), 37 had microinvasion. The DCIS group exhibited low, intermediate and high grades in 53.7%, 34.6% and 11.8% of cases, respectively, mostly with solid (43.4%) or cribriform (41.9%) pattern. Forty out of 43 invasive cases were invasive ductal carcinoma (IDC), mostly DCIS predominant. Immunophenotypically, luminal A phenotype was identified in 55.1%, 63.2% and 45.0% of DCIS, LCIS and IDC cases, respectively. Topographical type A group (carcinoma being entirely confined to SA, n=176) was characterised by smaller size, less invasiveness, lower grade and more frequency of luminal A immunophenotype compared with type B group (≥ 50% but not all of the carcinomatous lesion being located in SA, n=30) (all P<0.05)., Conclusions: CIS, especially non-high-grade DCIS, represents the most common variant of SA-BC, and luminal A is the most predominant immunophenotype. CNB assessment might be challenging in some SA-BCs. The topographical pattern has great clinicopathological relevance. Careful evaluation of the contralateral breast and long-term follow-up for patients with SA-BC is necessary given its high prevalence of bilaterality., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.

Context.--The updated American Society of Clinical Oncology/College of American Pathologists guideline for human epidermal growth factor receptor 2 (HER2) testing in breast cancer requires pathologists to re-evaluate HER2 status. Objective.--To define HER2 status of breast cancer using immunohistochemistry and fluorescence in situ hybridization. Design.--Diagnostic reports of invasive breast cancers made between 2014 and 2018 with HER2 immunohistochemistry and fluorescence in situ hybridization results were retrieved. HER2 status was re-defined using the updated recommendations. Results.--Of 2514 tumors, 89.7% (2254 of 2514) suggested for fluorescence in situ hybridization assay were HER2 immunohistochemistry 2+. Approximately 8.9% (225 of 2514) and 1.4% (35 of 2514) of tumors were of immunohistochemistry 0/1+ and 3+, respectively. Based on the average HER2 copy number and HER2:CEP17 ratio, tumors were assigned into 5 groups, including 13.1% (330 of 2514) group 1 tumors, 2.1% (52 of 2514) group 2 tumors, 1.1% (27 of 2514) group 3 tumors, 7.0% (175 of 2514) group 4 tumors, and 76.8% (1930 of 2514) group 5 tumors. In combination with immunohistochemistry, all tumors in group 2 and group 4 changed HER2 status, from positive and equivocal into negative, respectively, while group 3 tumors remained positive. Comparative analyses of clinicopathologic features of tumors in different groups revealed that group 2 and 4 tumors displayed worse clinicopathologic features than those of group 5, while group 3 tumors shared similar clinicopathologic features to those of group 1. Conclusions.--Following the updated guideline, HER2 status is clearly designated. Significant differences regarding clinical features were observed between tumors in different groups but they share the same HER2 status, suggesting further validation of the accuracy of this diagnostic approach is warranted. (Arch Pathol Lab Med. 2020;144:1097-1107; doi: 10.5858/arpa.2019-0369-OA), Human epidermal growth factor receptor 2 (HER2) status can be revealed by HER2 gene status tested by in situ hybridization (ISH) assay or HER2 protein expression assessed by immunohistochemistry (IHC). [...]

Aims: The protein expression of programmed death‐ligand 1 (PD‐L1) has been recognised as being a biomarker for poor prognosis in diffuse large B‐cell lymphoma (DLBCL). The aims of this study were to determine PD‐L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL. Methods and results: In this study, we used fluorescence in‐situ hybridisation, RNA in‐situ hybridisation and immunohistochemistry to determine PD‐L1 status at three different levels in 287 DLBCL samples with follow‐up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD‐L1 DNA amplification, 19.9% (57/287) had high PD‐L1 mRNA expression, and 11.8% (34/287) had high PD‐L1 protein expression. Both mRNA and protein expression of PD‐L1 were significantly higher in non‐germinal centre B‐cell‐like (GCB) DLBCL than in GCB DLBCL (P < 0.05). In addition, the patients with high PD‐L1 mRNA or high PD‐L1 protein expression but no PD‐L1 DNA amplification had significantly poorer overall survival (OS) than those with low PD‐L1 expression (P < 0.05). Furthermore, we found that PD‐L1 mRNA and PD‐L1 protein expression were highly correlated (P = 0.012), which was observed in all three samples with DNA amplification. Conclusions: PD‐L1 DNA amplification is a rare event, PD‐L1 mRNA is the main contributor to the high PD‐L1 protein expression, and the latter two will serve as important biomarkers for predicting the prognosis of DLBCL patients and selecting them for immunotherapy. [ABSTRACT FROM AUTHOR]

Aims: Pure mucinous carcinoma (PMC) of the breast is a low‐grade cancer. In this study, we aimed to elucidate the prognostic significance of micropapillary structures in breast PMC. Methods and results: Seventy‐five patients with breast PMC were recruited. All haematoxylin and eosin (H&)‐stained slides were reviewed, and clinicopathological features including age, tumour size, growth pattern, nuclear grade, histological grade, lymph node (LN) status, immunohistochemistry (IHC) staining of hormone receptor, human epidermal growth factor receptor 2 (HER2) expression and Ki‐67 proliferation index were analysed. Fluorescence in‐situ hybridisation (FISH) was used to verify the amplification of the HER2 gene in IHC 2+ cases. Seventy‐one cases of PMC were followed‐up from 18 to 110 months (median = 68 months). All PMC patients were female, aged 31–83 years (median = 57 years). All PMCs were nuclear grades 1 or 2. Oestrogen receptor was positive in all cases (100%) and progesterone receptor was positive in 68 cases (90.7%). There was no 3+ staining or gene amplification of HER2. Four patients had axillary LN metastasis (5.7%). Micropapillae were observed in 60 cases (80%) with varied percentages, and divided into five groups: 0%, <20%, 20–49%, 50–89% and ≥90%, with 15 (20%), 15 (20%), 17 (22.7%), 17 (22.7%) and 11 (14.7%) cases in each. Follow‐up results showed that neither recurrence nor distant metastasis occurred in all PMCs. Statistical analysis revealed that only larger tumour size was correlated significantly with LN metastasis (P < 0.05). Conclusions: The presence of nuclear grades 1 or 2 micropapillae, irrespective of the percentage, had no significant relationship with LN metastasis and patients' survival of PMC. [ABSTRACT FROM AUTHOR]

Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients’ clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS. [ABSTRACT FROM AUTHOR]

Aims: To analyse the clinicopathological, immunohistochemical and β-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST). Methods and results: Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. β-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T. Conclusions: MCST shows a unique morphology with characteristic immunophenotype. β-catenin expression in the nucleus and b-catenin mutations were identified in the majority of cases, which suggests that the Wnt/β-catenin pathway may play a crucial role in the tumorigenesis of MCST. [ABSTRACT FROM AUTHOR]

Objective: We elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers. Materials and Methods: Forty-nine rectal cancer patients who received surgical resection without neoadjuvant therapy were selected that underwent primary MRI and diffusion-weighted imaging (DWI). Tumor ADC values were determined and analyzed to identify any correlations between these values and pre-treatment CEA or CA19-9 levels, and/or the histological and immunohistochemical properties of the tumor. Results: Inter-observer agreement of confidence levels from two separate observers was suitable for ADC measurement (k  =  0.775). The pre-treatment ADC values of different T stage tumors were not equal (p  =  0.003). The overall trend was that higher T stage values correlated with lower ADC values. ADC values were also significantly lower for the following conditions: tumors with the presence of extranodal tumor deposits (p  =  0.006) and tumors with CA19-9 levels ≥ 35 g/ml (p  =  0.006). There was a negative correlation between Ki-67 LI and the ADC value (r  =  −0.318, p  =  0.026) and between the AgNOR count and the ADC value (r  =  −0.310, p  =  0.030). Conclusion: Significant correlations were found between the pre-treatment ADC values and T stage, extranodal tumor deposits, CA19-9 levels, Ki-67 LI, and AgNOR counts in our study. Lower ADC values were associated with more aggressive tumor behavior. Therefore, the ADC value may represent a useful biomarker for assessing the biological features and possible relationship to the status of identified rectal cancers. [ABSTRACT FROM AUTHOR]

Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic carcinoma. The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression profile of this rare tumor in Chinese population. Thirteen cases of MPC were evaluated using morphology observation and immunohistochemistry. All tumors had invasive carcinoma with an abrupt transition to chondromyxoid matrix without an intervening spindle cell sarcomatoid component. The distribution of tumor cells was diffuse in eight cases and peripheral in five cases. Matrix distribution was diffuse or multifocal. Necrosis was present in 11 cases. An overt invasive ductal carcinoma was observed in 11 cases and the other two tumors were consistent with MPC arising in microglandular adenosis. Ten of 13 cases were triple negative (ER-, PR-, Her2/neu-). Eight of 10 triple negative cases were cytokeratin 5/6, cytokeratin 14 or epidermal growth factor receptor positive, consistent with the basal-like phenotype. S-100 protein was positive in all cases. At the time of initial diagnosis, one of 13 patients had lung metastasis and axillary lymph nodes metastasis. Follow-up time ranged from 6 to 30 months. All patients remained alive. One patient developed a soft tissue metastasis 24 months after surgery. [ABSTRACT FROM AUTHOR]